Doctors find progesterone dosages confusing

Troches and creams are completely different dose forms and utilise different pathways to achieve systemic absorption.

In simple terms progesterone in a cream is absorbed through the skin, travels through the network of microcirculation, working its way into the larger blood vessels and reaches the liver where it is broken down into inactive metabolites and excreted.

Troches are taken under the tongue via what is called the buccal route. Buccal absorption works on the fact that under the tongue there is a very high concentration of large blood vessels very close to the surface and drugs can pass across the membranes into the general circulation. Glyceryl trinitrate in angina tablets have worked using this method for decades. The steroids in the troches pass into the circulation in a similar manner.

The reason for the dose differences between the two prepartions is the time and route the progesterone takes to get to the liver. Transdermal creams allow for greater amounts of body tissue to be exposed to the effects of progesterone than does the troche route because a large percentage of the troche gets to the liver quickly and is metabolised.

Another reason for troches having a larger dose of progesterone relative to the cream is because when the troche dissolves much of the saliva in which the contents of the troche are dispersed is swallowed. Once swallowed the hepatic first-pass effect (liver) inactivates the progesterone. As you are aware progesterone taken orally is essentially inactived by the liver before it can achieve any beneficial effects.

When Dr David Zava was in Melbourne 18 months or so ago he was asked a question from the floor about the percentage of progesterone absorbed from troches. He had no idea, but one of the compounding pharmacists made a guestimate of about 50%. Until someone does a proper study on the pharmacokinetics of the troche we won’t know.

What the only formal study with a progesterone troche has shown is that three hours after taking a troche dose levels have peaked and are back to baseline, hence troche dosing is often 3-4 times daily to achieve a sustained exposure to progesterone.

Creams on the other hand utilise fatty and cellular tissue as ‘resevoirs’ for storing progesterone which is why creams achieve a more sustained level of progesterone exposure. This ‘storage’was validated by Chang et al in their 1995 study utilising transdermal progesterone on women with breast cancer.

In short troches use more progesterone because a large amount is deactivated by the liver in a short period of time relative to creams. Creams use smaller amounts because it takes longer for these amounts to get to the liver and tissues are exposed to the progesterone for longer and hence have a greater capacity to take up and utilise the hormone.

Dr John Lee always based his dosing around the ovary’s ability to produce between 15-20mg of progesterone daily in a normal healthy woman. These women are exposed on a monthly basis to normal progesterone production and their body tissues are progesterone replete.

A progesterone deficient woman’s tissues are crying out for progesterone and I have found a Pro-Feme dose of around 32mg daily (2cm of 3.2% or 4cm of 1.6% Pro-Feme) will achieve a better and quicker clinical outcome in these women than drip feeding 5-10mg daily.

Michael Buckley
CEO of Lawley Pharmaceuticals

Founded in 1995 by pharmacist Michael Buckley, Lawley Pharmaceuticals has grown to become a world leader in research and development of transdermal hormone preparations.